Premium
Population Pharmacokinetics of Humanized Monoclonal Antibody HuCC49ΔCH2 and Murine Antibody CC49 in Colorectal Cancer Patients
Author(s) -
Fang Lanyan,
Holford Nicholas H. G.,
Hinkle George,
Cao Xianhua,
Xiao Jim J.,
Bloomston Mark,
Gibbs Seth,
Al Saif Osama Habib,
Dalton James T.,
Chan Kenneth K.,
Schlom Jeffery,
Martin Edward W.,
Sun Duxin
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006293758
Subject(s) - medicine , pharmacokinetics , population , volume of distribution , colorectal cancer , covariate , surgery , oncology , cancer , statistics , mathematics , environmental health
To predict the optimal time for surgery after antibody administration, the population pharmacokinetics of 125 I‐HuCC49ΔCH2 and 125 I‐CC49 were characterized in 55 patients with colorectal cancers. A 2‐compartment linear model was used to fit the pharmacokinetic data. Model stability and performance were assessed using a visual predictive check procedure. Different clinical trial designs were evaluated by simulation in combination with Bayesian estimation method to predict the optimal time for surgery. The results showed that HuCC49ΔCH2 had 65% faster clearance from blood circulation and 24% shorter mean residence time than CC49. Population pharmacokinetic analysis identified body weight as the only covariate to explain between‐subject variability in clearance, intercompartmental flow rate, and volume of distribution. Model predictions indicated a wide interval for the optimal time of surgery, suggesting that it would be beneficial to individualize the time of surgery for each patient by measurement of antibody disposition. Clinical trial designs with at least 3 measurements of antibody disposition were found to be better than an empirical direct observation method for the optimal prediction of surgery time.